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Synthesis And Biological Evaluation Of Novel Indomethacin Derivatives As Potential Anti‐Colon Cancer Agents

A. Farrag
Published 2016 · Chemistry, Medicine

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The molecular structure of indomethacin was used as a starting scaffold for the synthesis of 20 novel analogs and to study their effects on the proliferation of three human colon cancer cell lines, HCT‐116, HT‐29, and Caco‐2, by MTT assay. The synthesized indomethacin analogs were characterized on the basis of IR, 1H NMR, 13C NMR, mass spectral data, and elemental analysis results. Cytotoxicity assay results showed that the indomethacin amide analog 2 was the most potent anticancer agent (IC50 = 0.78, 0.09, and 0.0127 μg/mL) against the three colon cancer cell lines, respectively, being more potent than the standard 5‐fluorouracil (IC50 = 1.8, 0.75, and 5.45 μg/mL). Interestingly, the indomethacin oxazin analog 3 and the indomethacin amide analog 8 displayed very potent anticancer activity against the HCT‐116 cell line with IC50 = 0.421 and 0.27 μg/mL, respectively, much better than the reference (IC50 = 1.8 μg/mL). Additionally, analogs 3, 4b, 11, 12c, and 13a exhibited excellent antitumor activity against Caco‐2 cells, with IC50 ranging from 1.5 to 4.5 μg/mL. Furthermore, analogs 2 and 8 were additionally examined for their effect on the cell cycle of HCT‐116 and HT‐29 cells, respectively, using flow cytometric analysis. Analog 2 arrested the cell cycle of HT‐29 cells at the S phase, while 8 was found to arrest the cell cycle of HCT‐116 cells at the G0/G1 phase.
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